Opioids are a vital therapeutic intervention for pain control, anesthesia and gastrointestinal disorders. Opioids can also modulate the immune response. Given the high incidence of HIV infection in intravenous drug users (IDUs) and the observation that IDUs are prone to infectious disease, it is essential to determine the effects of opioids on the immune response. Although tolerance can develop to many opioid effects, evidence suggests that these "tolerant" animals are immunologically susceptible to the effects of stress. In order to understand how stress can alter the immune response of a morphine "tolerant" animal, I intend to: 1) characterize the immune response of morphine "tolerant" animals, 2) examine the immunological effects of diverse stressors on morphine "tolerant" animals, 3) characterize the immunomodulatory effects of withdrawal and the susceptibility to stress in previously dependent, drug-free animals, and 4) examine the sensitivity of morphine "tolerant" animals to additional drugs of abuse (pharmacological stressors). The broad goal of this research is to examine the potential immunological vulnerability of individuals chronically administered opioids. It is hoped that the information obtained will contribute to the development of rational therapeutic interventions that will both reduce the risk of therapeutic opioid use, and minimize the spread of infectious disease.